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排序方式: 共有67条查询结果,搜索用时 15 毫秒
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The effect of eight different acetylcholinesterase inhibitors (AChEIs) on the activity of acetylcholinesterase (AChE) molecular forms was investigated. Aqueous-soluble and detergent-soluble AChE molecular forms were separated from rat brain homogenate by sucrose density sedimentation. The bulk of soluble AChE corresponds to globular tetrameric (G4), and monomeric (G1) forms. Heptylphysostigmine (HEP) and diisopropylfluorophosphate were more selective for the G1 than for the G4 form in aqueous-soluble extract. Neostigmine showed slightly more selectivity for the G1 form both in aqueous- and detergent-soluble extracts. Other drugs such as physostigmine, echothiophate, BW284C51, tetrahydroaminoacridine, and metrifonate inhibited both aqueous- and detergent-soluble AChE molecular forms with similar potency. Inhibition of aqueous-soluble AChE by HEP was highly competitive with Triton X-100 in a gradient, indicating that HEP may bind to a detergent-sensitive non-catalytic site of AChE. These results suggest a differential sensitivity among AChE molecular forms to inhibition by drugs through an allosteric mechanism. The application of these properties in developing AChEIs for treatment of Alzheimer disease is considered.Special issue dedicated to Dr. Morris H. Aprison. 相似文献
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Kathleen L. Summers Dr. Patrick Lippiello Ezio Giacobini 《Neurochemical research》1996,21(10):1181-1186
Transcortical dialysis was employed to investigate the effects of subcutaneous (s.c.) injections of RJR-2403 (1.2–7.2 μmol/kg)
on extracellular levels of acetylcholine (ACh), norepinephrine (NE), dopamine (DA), and serotonin (5-HT) in rat. Systemic
administration of RJR-2403 produced a 90% increase of cortical extracellular ACh levels that persisted for up to 90 minutes
after injection. Norepinephrine and DA release were increased 124% and 131% above basal values, respectively. Serotonin (5-HT)
levels in the dialysate were also significantly elevated by RJR-2403 (3.6 μmol/kg, s.c.) 70% above baseline at 90 minutes
post-injection. Comparison of these responses to those of (−)nicotine from a previous study reveals little difference between
the two compounds in their ability to influence cortical neurotransmitter release following systemic administration. 相似文献
4.
P Gontero S Geuna A Poncino M G Giacobini Robecchi 《Bollettino della Società italiana di biologia sperimentale》1992,68(1):17-23
Amputation of the lizard tail is followed by its complete regeneration over a period of six-eight months. The new tail is innervated only by the last three pairs of spinal nerves upstream from the plane of amputation, since no nerve cells are present in the regenerated. The corresponding dorsal root ganglia increase in volume (hypertrophic ganglia) and most of their sensory neurons become hypertrophic. Satellite cells belonging to this hypertrophic ganglia increase in number. This paper describes an autoradiographic study, after administration of tritiated thymidine, of the hypertrophic dorsal root ganglia of the lizard during tail regeneration. We evaluated the number of satellite cells which neo-synthetize DNA ("labeling index = LI%) and are therefore suitable to undergo cell division. The LI% was significatively increased in hypertrophic ganglia when compared to internal control ganglia (not directly involved in the reinnervation process) and normal ganglia (lizards with intact tails). The comparison between internal control ganglia and normal ganglia showed higher LI% values in the formers, although this difference was not statistically significative. These results are in line with those obtained by other authors and suggest that satellite cells of dorsal root ganglia can undergo cellular proliferation also in the adult, especially in particular experimental conditions. 相似文献
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Following i.c.v. (intracerebral ventricular) injections ofd,l-[3H]pipecolic acid (PA), it is reabsorbed from the ventricles and redistributed to various brain regions. The highest accumulation is found in three brain regions ipsilateral to the injection site, hippocampus, neocortex, striatum, and in the diencephalon. Following preloading in vivo, the radioactivity is released from hippocampus slices in the perfusion medium after depolarization induced by high K+. During perfusion with a Ca++ free medium containing EGTA, a significant reduction of release is observed.The radioactivity ofd,l-[3H]PA in the brain shows a more rapid phase of decrease from 0 to 2 hours and a slower phase from 2 to 5 hours. At 5 hours, only 28% radioactivity, represented mainly by PA, is left in the brain. Kidney secretion represents the major route of elimination of the injected PA. The presence of -aminoadipic acid both in brain and urine was observed. Probenecid (200 mg/kg) significantly increases the accumulation of i.c.v. injectedd,l-[3H]PA in brain and kidney. The presence of a regional accumulation of PA in certain brain regions, its metabolism in brain, its enhanced retention following probenecid administration and its Ca++ dependent release following high K+ stimulation, all constitute indirect evidence for a neuronal localization of this brain endogenous iminoacid. 相似文献
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The existence of an Early Gravettian perforated human tooth at the abri Pataud came to light thanks to the reexamination of the osseous artefacts from the level 5. Even if the method of perforation of this tooth is analogous to the one used to pierce the animal teeth discovered in the same level, this pendant would have a particular meaning. 相似文献
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In an effort to develop an animal model of hyperpipecolatemia, the uptake of pipecolic acid (PA) in the brain and changes of PA levels in serum following administration ofd,l-PA were studied in the mouse using a new sensitive HPLC-EC method. Following i.p. injections (250 mg/kg) to adult male mice, the brain concentration peaks at 5–10 min (40 nmol/g). The level remains relatively stable up to 5 hrs and then declines slowly to 24 hrs. In serum, the level of PA increases rapidly to reach the maximum value at 10 min and then decreases rapidly in the first hour and continues to decline more slowly to 24 hrs. The net uptake of PA following administration of various amounts ofd,l-PA is saturable at low doses (3.9–15.6 mg/kg), and it increases linearly at higher doses in a dose-dependent manner up to the maximum dose (500 mg/kg) used in the present study. Kinetic analysis suggests the presence of two kinds of transport systems. These findings are in good agreement with the previous results usingd,l-[3H]PA in the mouse (7) andl-[14C]PA in the rat (13). There were no significant differences between uptake ofd-pipecolic acid andl-pipecolic acid (250 mg/kg, i. p., 10 min), suggesting the absence of stereospecificity for PA uptake in the mouse brain. Developmental changes in net brain uptake of PA following injections ofd,l-PA (250 mg/kg, s.c., 10 min) showed an age-dependent decrease which continues until adult levels are reached at four weeks after birth. The results suggest that the blood brain barrier (BBB) for PA is completed during the first month of life. Following administration ofd,l-PA (250 mg/kg, s.c.) to pregnant mice during the period 19–21 days of gestation, PA level increases in fetal brain to a maximum value at 2 hrs (420 nmol/g). This level is unchanged during 24 hrs. The maximum level of PA in fetal serum is reached at 30 min to 1 hr. The level gradually decreases after 1 hr over 24 hrs. These results indicate that PA taken up by the placenta and into the brain is transported from the fetal circulation. Our results also demonstrate that a higher amount of PA is taken up by the fetal than the adult brain. This finding is important in order to develop an animal model of hyperpipecolatemia in which high brain levels of PA should mimick those of human hyperpipecolatemic patients. Our results strongly support the hypothesis that high levels of PA present in brain during fetal life may exert a devastating effect on the development of the human CNS in hyperpipecolatemic children. 相似文献